Approximately one third of all protein bind metal ions.Such metalloproteins play crucial roles in a large number of biological processes including the storage and transduction of energy, gene regulation, and metabolism. In order for these proteins to achieve their proper functions, they must selectively bind their cognate metal ions. Such recognition processes have been generally assumed to be governed by simple, thermodynamically controlled, binding reactions. Evidence has been accumulating revealing the importance of kinetic factors as well. The kinetics of metal binding and exchange reactions have not been extensively studied. The thermodynamics and kinetics of metal binding reactions appear to be significantly affected by the degree of structure that remains in the protein upon removal of the metal ion. The thermodynamics and kinetics of metal binding, release, and exchange reactions will be studied for a series of protein that differ in terms of these structural characteristics. Systems for which protein folding is induced only upon metal binding offer unique opportunities for investigating both metal binding and protein folding processes. Such studies will be performed with the use of a so- called zinc finger peptide. Aspects of protein folding to be investigated include the thermodynamic propensities for different amino acids to adopt beta sheet, alpha helix, and other structures. The data obtained will be interpreted in terms of a structure-based thermodynamics analysis model that has been developed for studies of other protein folding and binding reactions. Finally, the ability to modulate metal binding affinity through variations in protein folding energies will be utilized to generate a series of peptide sensors to be used to monitor zinc and other metal ion concentrations via changes in fluorescence.